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  • 1
    In: British Journal of Pharmacology, Wiley, Vol. 178, No. 17 ( 2021-09), p. 3570-3586
    Abstract: Dopamine agonists targeting D 2 receptor have been used for decades in treating pituitary adenomas. There has been little clear evidence implicating the canonical G protein signalling as the mechanism by which D 2 receptor suppresses the growth of pituitary tumours. We hypothesize that β‐arrestin2‐dependent signalling is the molecular mechanism dictating D 2 receptor inhibitory effects on pituitary tumour growth. Experimental Approach The involvement of G protein and β‐arrestin2 in bromocriptine‐mediated growth suppression in rat MMQ and GH3 tumour cells was assessed. The anti‐growth effect of a β‐arrestin2‐biased agonist, UNC9994, was tested in cultured cells, tumour‐bearing nude mice and primary cultured human pituitary adenomas. The effect of G protein signalling on tumour growth was also analysed by using a G protein‐biased agonist, MLS1547, and a Gβγ inhibitor, gallein, in vitro . Key Results β‐arrestin2 signalling but not G protein pathways mediated the suppressive effect of bromocriptine on pituitary tumour growth. UNC9994 inhibited pituitary tumour cell growth in vitro and in vivo . The suppressive function of UNC9994 was obtained by inducing intracellular reactive oxygen species generation through downregulating mitochondrial complex I subunit NDUFA1. The effects of Gαi/o signalling and Gβγ signalling via D 2 receptor on pituitary tumour growth were cell‐type‐dependent. Conclusion and Implications Given the very low expression of Gαi/o proteins in pituitary tumours and the complexity of the responses of pituitary tumours to G protein signalling pathways, our study reveals D 2 receptor β‐arrestin2‐biased ligand may be a more promising choice to treat pituitary tumours with improved therapeutic selectivity.
    Type of Medium: Online Resource
    ISSN: 0007-1188 , 1476-5381
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 2029728-2
    SSG: 15,3
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  • 2
    In: Nutrition & Diabetes, Springer Science and Business Media LLC, Vol. 13, No. 1 ( 2023-04-08)
    Abstract: Lentinan (LNT) is a complex fungal component that possesses effective antitumor and immunostimulating properties. However, there is a paucity of studies regarding the effects and mechanisms of LNT on type 1 diabetes. Objective In the current study, we investigated whether an intraperitoneal injection of LNT can diminish the risk of developing type 1 diabetes (T1D) in non-obese diabetic (NOD) mice and further examined possible mechanisms of LNT’s effects. Methods: Pre-diabetic female NOD mice 8 weeks of age, NOD mice with 140–160 mg/dL, 200–230 mg/dL or 350–450 mg/dL blood glucose levels were randomly divided into two groups and intraperitoneally injected with 5 mg/kg LNT or PBS every other day. Then, blood sugar levels, pancreas slices, spleen, PnLN and pancreas cells from treatment mice were examined. Results Our results demonstrated that low-dosage injections (5 mg/kg) of LNT significantly suppressed immunopathology in mice with autoimmune diabetes but increased the Foxp3+ regulatory T cells (Treg cells) proportion in mice. LNT treatment induced the production of Tregs in the spleen and PnLN cells of NOD mice in vitro. Furthermore, the adoptive transfer of Treg cells extracted from LNT-treated NOD mice confirmed that LNT induced Treg function in vivo and revealed an enhanced suppressive capacity as compared to the Tregs isolated from the control group. Conclusion LNT was capable of stimulating the production of Treg cells from naive CD4 + T cells, which implies that LNT exhibits therapeutic values as a tolerogenic adjuvant and may be used to reverse hyperglycaemia in the early and late stages of T1D.
    Type of Medium: Online Resource
    ISSN: 2044-4052
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 2609314-5
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  • 3
    In: Journal of Biomedical Nanotechnology, American Scientific Publishers, Vol. 16, No. 3 ( 2020-03-01), p. 352-363
    Abstract: Pancreatic ductal adenocarcinoma (PDAC) is radioresistant. Due to their strong X-ray absorption capacity, gold nanoparticles (AuNPs) have been used as radiosensitizers for cancer therapeutics. Herein, we describe a novel conjugate complex consisting of a peptide for targeting plectin-1 (PTP) specifically expressed on the PDAC cell membrane and AuNPs, termed AuNP-PTP, to be used for PDAC radiotherapy in vitro and in vivo . Previous studies revealed that compared with unmodified AuNPs, AuNP-PTP along with relevant low-energy X-ray irradiation of 6 MV at a dose of 2 Gy (RF) increased the targeting efficiency and induced apoptosis in treated PANC-1 cells and tumours. Importantly, extensive histopathological examination did not reveal evidence of acute or chronic injury in mice due to AuNPs or AuNP-PTP for up to six weeks despite the presence of X-ray exposure. The delicate AuNP-PTP hybrid provides a novel strategy to enhance radiotherapy efficiency in PDAC treatment.
    Type of Medium: Online Resource
    ISSN: 1550-7033
    Language: English
    Publisher: American Scientific Publishers
    Publication Date: 2020
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